Synaptic Release of Acetylcholine Rapidly Suppresses Cortical Activity by Recruiting Muscarinic Receptors in Layer 4
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Abstract
Abstract Basal forebrain (BF) cholinergic projections to neocortex dynamically regulate information processing. However, the underlying synaptic and cellular mechanisms remain poorly understood. While synaptically released acetylcholine (ACh) can recruit nicotinic ACh receptors (nAChRs) expressed in distinct types of interneurons, previous work has not defined a clear role for muscarinic ACh receptors (mAChRs) in the fast cholinergic control of cortical activity. To address this question, we employed a slice model of cortical activity and used optogenetics to selectively activate cholinergic afferents. We found that transient ACh increases led to a rapid and persistent suppression of cortical activity, mediated by mAChRs in layer 4 and by nAChRs in layer 2/3. Furthermore, mAChR-dependent cholinergic control was mediated at least in part by a short-latency and long-lasting inhibition of layer 4 excitatory neurons. Thus, the activation of postsynaptic mAChRs is central to the flexible cholinergic control of cortical activity.
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Optical stimulation of endogenous ACh release in S1 leads to activation of mAChRs on excitatory and inhibitory neurons in L4 and activation of nAChRs, presumably on inhibitory interneurons, in superficial layers, causing overall suppression of cortical activity.
“Optical stimulation of endogenous ACh release in S1 leads to activation of mAChRs on excitatory and inhibitory neurons in L4 and activation of nAChRs, presumably on inhibitory interneurons, in the superficial layers, causing overall suppression of cortical activity184.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [184]
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References 73 · Cited by 47
- Authors
- Dasgupta, R., Seibt, F., & Beierlein, M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas Health Science Center at Houston (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2018-05-08
- Volume
- 38
- Issue
- 23
- Pages
- 5338-5350
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC5990982
- OpenAlex
- W2794149787
- Cited by
- 47
- References
- 73
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 9 · 2022: 3 · 2021: 3 · 2020: 10 · 2019: 6 · 2018: 3
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS077989)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- acetylcholine, muscarinic receptors, nicotinic acetylcholine receptors, cholinergic afferents, basal forebrain, somatosensory cortex, cortical layer 4, cortical inhibition, cortical interneurons, excitatory neurons, sensory processing
- MeSH terms
- Acetylcholine, Animals, Female, Male, Mice, Transgenic, Nerve Net, Synaptic Transmission, Organ Culture Techniques, Receptors, Muscarinic, Receptors, Nicotinic, Somatosensory Cortex
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